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Competing Interests: Declaration of interests CL reports royalties from Western Psychological Services for diagnostic instruments; is on scientific advisory boards or projects for Tilray, Roche, Gateway, Springtide, and Greenwich Biosciences; and is supported by grants from the US National Institute of Mental Health (R01HD081199, R01MH115363, R01MH104423–02, and R01MH114925). TCh reports consultancy fees from Roche and Servier; royalties from Sage Publications and Guilford Publications; grants from the UK Medical Research Council (grants number MR/K021389/1 and MR/R011427/1), the UK National Institute for Health Research (grants number 13/119/18 and RP-PG-1211–20016), the EU Horizon 2020 programme (grant number 814302), Innovative Medicines Initiative (grant agreement number 777394 and AIMS-2-TRIALS, which receives support from the EU Horizon 2020 programme, European Federation of Pharmaceutical Industries and Associations, Autism Speaks, Autistica, and Simons Foundation Autism Research Initiative); and grant support from MQ Mental Health Research, The Waterloo Foundation, Epilepsy Research UK, the Charles Hawkins Fund, and the Baily Thomas Foundation. EA reports consulting fees from Roche and Quadrant; funding from Roche and SynapDx; non-financial support from AMO Pharma; book royalties from APPI and Springer; editorial board honoraria from Wiley; a patent (US20160000365A1) for an anxiety meter; is supported by the Ontario Brain Institute (POND network), Canadian Institutes of Health Research, Autism Intervention Research Network on Physical Health (funded by the Health Resources and Services Administration), US National Institutes of Health, Brain Canada, and the Azrieli Foundation; and is the Canada Research Chair in translational therapeutics in autism spectrum disorder and Dr Stuart D Sims endowed chair in Autism. BB is supported by US National Institute of Mental Health grant (1R01HD82127). AHa was supported by grants from the South-Eastern Norway Regional Health Authority (grant numbers 2018059 and 2020022) and by the Research Council of Norway (grants number 274611 and 288083). RJ reports funding from Australia's National Health and Medical Research Council. JC is supported by National Institute of Mental Health grants NIMH09902, NIMH081148, NIMH083707, NIMH80011, and U10MH66764. PC is supported by Simons Foundation Powering Autism Research and the Maternal and Child Health Bureau of the Leadership Education in Neurodevelopmental Disability. TCa reports personal fees from Western Psychological Services. LS reports being a consultant for Roche, Yamo, Teva, Impel, and Janssen Pharmaceuticals; book royalties from Oxford University Press, Guilford Press, and American Psychological Association Press; and licensing royalties for the Parent-Rated Anxiety Scale for Autism Spectrum Disorder from Cogstate and Yamo. PPW reports being employed by Clinical Research Associates, a non-profit organisation that is developing an experimental drug treatment for autism. CMF receives royalties for books on autism spectrum disorder, attention-deficit hyperactivity disorder, and major depressive disorder; grants for the A-FIPP randomised controlled trial (FR2069/8–1, 8-2), awarded by the German Research Foundation, and for the EU-AIMS2-TRIALS (H2020 777394) and EU STIPED (H2020 731827), awarded by the EU. CK is supported by grants from the Health Resources and Services Administration of the US Department of Health and Human Services (UA3MC11055), the US National Institutes of Health (R01HD098248, R01HD095973, P50DC018006), the US Department of Defense, and the Goldman Foundation (3104). APi receives questionnaire royalties from WPS. AHo reports personal fees from GW Pharmaceuticals. PSz receives research funding from the Canadian Institutes of Health Research and royalties from Guilford Press and Simon & Schuster for books. PSh reports support from the Health Resources and Services Administration of the US Department of Health and Human Services under the Autism Transitions Research Project (UJ2MC31073). VS is supported by the National Institute for Health Research (grant numbers EME 13/119/18, RP-PG-1211–20016, and 15/162) and a grant from Autistica (number 7262). GD reports grants from the UK Medical Research Council and Grand Challenges Canada, outside the submitted work. All other authors declare no competing interests.

Background: It is not known whether early intervention can improve long-term autism symptom outcomes. We aimed to follow-up the Preschool Autism Communication Trial (PACT), to investigate whether the PACT intervention had a long-term effect on autism symptoms and continued effects on parent and child social interaction., Methods: PACT was a randomised controlled trial of a parent-mediated social communication intervention for children aged 2-4 years with core autism. Follow-up ascertainment was done at three specialised clinical services centres in the UK (London, Manchester, and Newcastle) at a median of 5·75 years (IQR 5·42-5·92) from the original trial endpoint. The main blinded outcomes were the comparative severity score (CSS) from the Autism Diagnostic Observation Schedule (ADOS), the Dyadic Communication Assessment Measure (DCMA) of the proportion of child initiatiations when interacting with the parent, and an expressive-receptive language composite. All analyses followed the intention-to-treat principle. PACT is registered with the ISRCTN registry, number ISRCTN58133827., Findings: 121 (80%) of the 152 trial participants (59 [77%] of 77 assigned to PACT intervention vs 62 [83%] of 75 assigned to treatment as usual) were traced and consented to be assessed between July, 2013, and September, 2014. Mean age at follow-up was 10·5 years (SD 0·8). Group difference in favour of the PACT intervention based on ADOS CSS of log-odds effect size (ES) was 0·64 (95% CI 0·07 to 1·20) at treatment endpoint and ES 0·70 (95% CI -0·05 to 1·47) at follow-up, giving an overall reduction in symptom severity over the course of the whole trial and follow-up period (ES 0·55, 95% CI 0·14 to 0·91, p=0·004). Group difference in DCMA child initiations at follow-up showed a Cohen's d ES of 0·29 (95% CI -0.02 to 0.57) and was significant over the course of the study (ES 0·33, 95% CI 0·11 to 0·57, p=0·004). There were no group differences in the language composite at follow-up (ES 0·15, 95% CI -0·23 to 0·53)., Interpretation: The results are the first to show long-term symptom reduction after a randomised controlled trial of early intervention in autism spectrum disorder. They support the clinical value of the PACT intervention and have implications for developmental theory., Funding: Medical Research Council., (Copyright © 2016 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY license. Published by Elsevier Ltd.. All rights reserved.)

Background: Results of small trials suggest that early interventions for social communication are effective for the treatment of autism in children. We therefore investigated the efficacy of such an intervention in a larger trial., Methods: Children with core autism (aged 2 years to 4 years and 11 months) were randomly assigned in a one-to-one ratio to a parent-mediated communication-focused (Preschool Autism Communication Trial [PACT]) intervention or treatment as usual at three specialist centres in the UK. Those assigned to PACT were also given treatment as usual. Randomisation was by use of minimisation of probability in the marginal distribution of treatment centre, age (42 months), and autism severity (Autism Diagnostic Observation Schedule-Generic [ADOS-G] algorithm score 12-17 or 18-24). Primary outcome was severity of autism symptoms (a total score of social communication algorithm items from ADOS-G, higher score indicating greater severity) at 13 months. Complementary secondary outcomes were measures of parent-child interaction, child language, and adaptive functioning in school. Analysis was by intention to treat. This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN58133827., Results: 152 children were recruited. 77 were assigned to PACT (London [n=26], Manchester [n=26], and Newcastle [n=25]); and 75 to treatment as usual (London [n=26], Manchester [n=26], and Newcastle [n=23]). At the 13-month endpoint, the severity of symptoms was reduced by 3.9 points (SD 4.7) on the ADOS-G algorithm in the group assigned to PACT, and 2.9 (3.9) in the group assigned to treatment as usual, representing a between-group effect size of -0.24 (95% CI -0.59 to 0.11), after adjustment for centre, sex, socioeconomic status, age, and verbal and non-verbal abilities. Treatment effect was positive for parental synchronous response to child (1.22, 0.85 to 1.59), child initiations with parent (0.41, 0.08 to 0.74), and for parent-child shared attention (0.33, -0.02 to 0.68). Effects on directly assessed language and adaptive functioning in school were small., Interpretation: On the basis of our findings, we cannot recommend the addition of the PACT intervention to treatment as usual for the reduction of autism symptoms; however, a clear benefit was noted for parent-child dyadic social communication., Funding: UK Medical Research Council, and UK Department for Children, Schools and Families., (Copyright 2010 Elsevier Ltd. All rights reserved.)